Trulicity® (dulaglutide) and the kidneys

Two different kidney messages in the documents

The first message is a warning. Section 5.5 of the US label reports acute kidney injury after approval in people on GLP-1 receptor agonists, Trulicity® included, sometimes severe enough to need haemodialysis, with most cases in people whose nausea, vomiting or diarrhoea had left them dehydrated. ^[1] The second is about people who already have reduced kidney function: Trulicity® was studied across the range, including a dedicated trial in moderate to severe chronic kidney disease, and the US label found no overall differences in safety or effectiveness by kidney function. ^[1]

From an upset stomach to a struggling kidney

The chain the labels describe has three links. The first is the stomach and bowel reactions that are Trulicity®’s most frequent side effects. In the US pool of placebo-controlled trials, 1,670 adults took Trulicity® and 568 took placebo; nausea, diarrhoea and vomiting all rose with dose, as the table shows. ^[1] The second link is dehydration: MedlinePlus explains that vomiting and diarrhoea drain fluid, and that feeling sick also makes people drink less. ^[10] The third is the kidney itself. When blood pressure falls because the body is short of fluid, less blood reaches the kidneys, which is one of the recognised causes of acute kidney failure. ^[9]

Timing matters. The US label asks for kidney function to be checked in anyone with fluid-losing reactions, especially when treatment begins and when the dose is increased, and Europe says reports clustered at the start of treatment. ^[1][3] The Canadian patient information goes further than the others: dehydration can cause serious kidney problems even in people whose kidneys were normal. ^[4] How often it happens is not known. In a pooled analysis of nine phase 2 and 3 trials, several of whose authors worked for Lilly, adverse events that could reflect acute kidney failure were recorded at 3.4 per 1,000 patient-years on dulaglutide, 1.7 on active comparators and 7.0 on placebo. ^[7]

What the long trials measured

REWIND, the heart-outcomes trial, followed 9,901 adults for a median of 5.4 years and measured kidney markers every year. In a Lilly-funded exploratory analysis, a combined outcome of new heavy albuminuria, a sustained fall in eGFR of 30% or more, or chronic dialysis or transplant occurred in 848 people (17.1%) on dulaglutide 1.5 mg against 970 (19.6%) on placebo, a hazard ratio of 0.85. ^[5] Most of that difference came from fewer new cases of heavy protein in the urine (hazard ratio 0.77). The separate results for eGFR decline (0.89) and for chronic kidney replacement (0.75) were not statistically significant. ^[5] Exploratory analyses generate questions; they do not establish a treatment effect.

Two further studies looked at kidney function directly. AWARD-7, an open-label trial in 577 adults with stage 3 to 4 chronic kidney disease, compared dulaglutide with insulin glargine, all with mealtime insulin, for 52 weeks. ^[6] At week 52, eGFR measured by cystatin C was 34.0 on 1.5 mg and 33.8 on 0.75 mg against 31.3 on glargine, while the fall in urine albumin did not differ significantly; end-stage kidney disease occurred in 4%, 7% and 8% respectively. ^[6] Across nine earlier trials pooled together, eGFR did not differ from placebo, active comparators or insulin glargine, and urine albumin was slightly lower. ^[7]

The newest data come from SURPASS-CVOT, where dulaglutide 1.5 mg was the active comparator rather than the test medicine. Over a median of four years, major kidney events occurred in 6.0% on tirzepatide against 7.6% on dulaglutide, a hazard ratio of 0.77. ^[8] Because there was no placebo group, this tells you how the two medicines compare, not whether dulaglutide itself changes kidney outcomes. None of these studies has given Trulicity® a kidney indication: the US label covers blood sugar control and lowering cardiovascular risk only. ^[1]

Living with chronic kidney disease on Trulicity®

The US label’s dedicated kidney trial enrolled people with an average eGFR of 38, 30% below 30 and 45% with heavy albuminuria; its main blood sugar results were measured at 26 weeks. ^[1] Blood levels of dulaglutide were modestly higher with kidney impairment, by 12% to 28% depending on the group, and the 52-week kidney trial showed drug behaviour similar to earlier studies. ^[1] In REWIND, half of the 9,713 people with a known eGFR had mildly reduced kidney function, 21.6% moderately and 1.1% severely reduced, and Canada reports no overall safety or efficacy differences between people above and below an eGFR of 60. ^[1][4]

Results from the kidney trial show what clinicians watch. In the Canadian monograph, a rise in blood creatinine was the most frequently reported event across all three groups, including insulin, at 40.3%, and a reported fall in GFR at 10.4%; stopping because of side effects was more common on dulaglutide (10.0% and 12.5%) than on glargine (6.2%). ^[4] Europe reports fewer symptomatic low blood sugar episodes on dulaglutide than on glargine in that trial, 4.44 and 4.34 against 9.62 per patient per year. ^[3]

Other things that strain the kidneys

MedlinePlus lists many causes of sudden kidney injury besides dehydration: very low blood pressure from bleeding, burns or severe infection, blockage of the urinary tract, kidney infections, and medicines including NSAID pain relievers, some antibiotics and blood pressure medicines, and contrast dye used in scans. ^[9] People with diabetes often take several of these, which is why a full medicine review is part of any kidney check.

Kidney stones are a different problem. MedlinePlus names not drinking enough fluids as the biggest risk factor and describes sudden severe pain in the side or back that may move to the groin, sometimes with blood in the urine. ^[11] The Canadian trial table records kidney stones slightly more often on Trulicity® than on placebo, but that table counts every event during treatment whether or not the medicine caused it, and the US and EU lists do not include stones. ^[4][1][3]

Keeping fluids up when side effects strike

The Medication Guide asks you to drink fluids to lower the chance of dehydration and to tell your healthcare provider right away about nausea, vomiting or diarrhoea that does not go away. ^[2] The EU leaflet makes the same point for the start of treatment and asks you to contact your doctor with any concerns. ^[3] A 2025 Mayo Clinic Proceedings review of digestive side effects of GLP-1 medicines puts adequate hydration alongside smaller, more frequent meals as first steps. ^[12]

MedlinePlus suggests drinking plenty every day, more in hot weather or with exercise, and with fever, vomiting or diarrhoea starting before any sign of dehydration appears. When you are struggling, it describes sipping water, sucking ice chips or drinking water or sports drinks with electrolytes, warns against salt tablets, and advises calling a provider early if dehydration looks likely. ^[10] If you use pain relievers such as ibuprofen while ill, ask your pharmacist or prescriber whether they suit you, since MedlinePlus lists NSAIDs among medicines that can harm the kidneys. ^[9]

Trulicity® is a registered trademark of Eli Lilly and Company. PepLabo is not affiliated with or endorsed by Eli Lilly and Company.